A Phase 1, Dose-Finding Study of Folotyn® (Pralatrexate Injection) Plus Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone (CHOP) in Patients With Peripheral T-Cell Lymphoma (PTCL)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 48
- 试验地点
- 4
- 主要终点
- Maximum Tolerated Dose
研究概览
简要总结
The purpose of this study is to evaluate the Maximum Tolerated Dose (MTD) of pralatrexate in combination with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) regimen in patients with newly diagnosed peripheral T-cell lymphoma (PTCL).
详细描述
This is a Phase 1, open-label, multicenter, two-part, dose-finding, dose-escalation study.
The study is divided into two parts:
Part 1
Up to five sequential dose cohorts will enroll a maximum of 6 patients each. Escalation of the pralatrexate dose, after CHOP administration (Fol-CHOP), will continue in a traditional 3+3 design, until determination of the MTD. If the MTD is not reached, the Maximum Administered Dose (MAD) of pralatrexate in combination with CHOP will be 30 mg/m2 IV on Days 1 and 8 of each 21-day cycle for up to 6 cycles.
The first cohort will begin with three patients with dose A and CHOP at full dose. If none of the first three patients experiences a Dose-Limiting Toxicity (DLT), the next three patients will be enrolled in next higher dose cohort. If one of the first three patients in the first cohort experiences DLTs, an additional three patients will be enrolled into that cohort. If 2 or 3 of the first 3 patients experience DLTs, then the MTD is not found.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 18 years or above
- •Adequate hematologic, hepatic, and renal function
- •Histologically confirmed, new diagnosis of PTCL
- •Eligible for CHOP regimen
- •Measurable disease based on Cheson 2007 criteria
- •Eastern Cooperative Oncology Group (ECOG) performance status < 2
- •Willing to perform at least two methods of contraception
- •Negative pregnancy test of females with childbearing potential.
排除标准
- •Active concurrent malignancy (except non melanoma skin cancer or carcinoma in situ of the cervix) or life threatening disease. If there is a history of prior malignancies or life threatening diseases, the patient must be disease free for at least 5 years.
- •Congestive heart failure Class III/IV according to the New York Heart Association (NYHA) Functional Classification.
- •Uncontrolled hypertension
- •Central nervous system (CNS) metastases .
- •Active uncontrolled infection, underlying medical condition, or other serious illness that would impair the ability of the patient to receive protocol treatment
- •Major surgery within 30 days prior to enrollment.
- •Use of any investigational drugs, biologics, or devices within 30 days prior or during the study treatment.
- •Previous exposure to pralatrexate.
- •Pregnant or breastfeeding.
研究组 & 干预措施
Part 1: Dose Finding, Cohort 1
Dose finding Phase Intervention: Folotyn (Pralatrexate Injection) CHOP: Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone
The first cohort will begin with three patients with dose A of pralatrexate plus CHOP at full dose.
The second cohort will begin with three patients with dose B of pralatrexate plus CHOP at full dose.
The third cohort will begin with three patients with dose C of pralatrexate plus CHOP at full dose.
The fourth cohort will begin with three patients with dose D of pralatrexate plus CHOP at full dose.
The fifth cohort will begin with three patients with dose E of pralatrexate plus CHOP at full dose.
Part 2: Dose Expansion, Additional ten patients will be enrolled at the MTD or MAD (if the MTD is not reached) plus CHOP at full dose in this part of the study. Blood samples for PK analysis of pralatrexate will be collected at various intervals pre and post pralatrexate injection during cycle 1, Dose 1.
干预措施: Pralatrexate Injection (Drug)
结局指标
主要结局
Maximum Tolerated Dose
时间窗: 126 Days
To evaluate the Maximum Tolerated Dose (MTD) of pralatrexate in combination with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) regimen in patients with newly diagnosed peripheral T-cell lymphoma (PTCL)
次要结局
- Number of participants with treatment emergent adverse events (TEAEs) using CTCAE version 4.03(126 Days)
- Objective Response Rate(126 Days)
- Plasma concentration of pralatrexate in combination with CHOP(126 Days)
- Pharmacokinetics: Area Under the Curve (AUC)(126 Days)
- Pharmacokinetics: Maximum Concentration (Cmax)(126 Days)
- Pharmacokinetics: Time to Maximum concentration (Tmax)(126 Days)
- Pharmacokinetics: Clearance (CL)(126 Days)